The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions

Abstract

Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

An Integrated Approach to Unravel Hidradenitis Suppurativa Etiopathogenesis

“…In the third study, Hessam et al (87) enrolled HS and psoriasis patients as well as healthy controls analyzed the expression profile of RNA-induced silencing complex (98) components (specifically, transactivation-responsive RNAbinding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component- 2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1)), also in this case using RT QPCR, in their inflamed tissues (skin biopsies). The authors concluded, after RISC component comparison between skin biopsies of HS and psoriasis patients and healthy controls, that all RISC components were differentially expressed thus highlighting a possible role in the modulation of skin inflammation in HS patients.…”

“…Another important aspect of gene expression regulation has been widely considered by Hessam et al (85–87); in three independent studies, the authors analyzed miRNA expression profiles in inflammatory lesions from HS patients.…”

Proceeding report of the third symposium on Hidradenitis Suppurativa advances (SHSA) 2018

“…MicroRNAs (miRNAs) are small molecules that negatively regulate gene expression and serve as effective biomarkers due to their abundance, cell‐type and disease‐stage specificity, and stability in clinical samples. Prior studies showed that miRNA processing factors (including Drosha and Dicer), as well as components of the RISC complex (AGO proteins), are distinctly and progressively downregulated from normal, perilesional, to lesional HS skin. The presence of many inflammatory miRNAs in lesional HS suggests a typical inflammatory response obscuring keratinocyte contribution .…”

Proceeding report of the Fourth Symposium on Hidradenitis Suppurativa Advances 2019

“…Previous studies have shown that various inflammation-associated microRNAs (miRNAs) such as Drosha and Dicer are dysregulated in HS. [12][13][14] Dr Thomas Meyer showed that the downregulation of Drosha and Dicer observed in HS appears to be independent of promotor methylation/epigenetic modifications. Finally, Dr Katherine Hallock discussed the high rates of emergency department use in pediatric patients with HS.…”